Cystic Fibrosis: Systems Biology Analysis from Homozygous p.Phe508del Variant Patients' Samples Reveals Perturbations in Tissue-Specific Pathways.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34901273", "kind": "science-record", "revision": 5, "content_hash": "sha256:17adc41f330103cd113804d1434790bca7a223934018aec3664771a13b574065", "created_at": "2026-11-01T17:36:37Z", "updated_at": "2026-11-01T22:48:03Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Cystic Fibrosis: Systems Biology Analysis from Homozygous p.Phe508del Variant Patients' Samples Reveals Perturbations in Tissue-Specific Pathways.", "doi": "10.1155/2021/5262000", "pmid": "34901273", "authors": ["Joice de Faria Poloni", "Thaiane Rispoli", "Maria Lucia Rossetti", "Cristiano Trindade", "José Eduardo Vargas"], "journal": "BioMed research international", "year": 2021, "abstract": "Cystic fibrosis (CF) is an autosomal recessive disorder, caused by diverse genetic variants for the CF transmembrane conductance regulator (CFTR) protein. Among these, p.Phe508del is the most prevalent variant. The effects of this variant on the physiology of each tissue remains unknown. This study is aimed at predicting cell signaling pathways present in different tissues of fibrocystic patients, homozygous for p.Phe508del. The study involved analysis of two microarray datasets, E-GEOD-15568 and E-MTAB-360 corresponding to the rectal and bronchial epithelium, respectively, obtained from the ArrayExpress repository. Particularly, differentially expressed genes (DEGs) were predicted, protein-protein interaction (PPI) networks were designed, and centrality and functional interaction networks were analyzed. The study reported that p.Phe508del-mutated CFTR-allele in homozygous state influenced the whole gene expression in each tissue differently. Interestingly, gene ontology (GO) term enrichment analysis revealed that only \"neutrophil activation\" was shared between both tissues; however, nonshared DEGs were grouped into the same GO term. For further verification, functional interaction networks were generated, wherein no shared nodes were reported between these tissues. These results suggested that the p.Phe508del-mutated CFTR-allele in homozygous state promoted tissue-specific pathways in fibrocystic patients. The generated data might further assist in prediction diagnosis to define biomarkers or devising therapeutic strategies.", "claims": [{"id": "claim-method", "statement": "The analysis for differentially expressed genes (DEGs) was performed using the R package limma, wherein ∣log2FC | >0.5 and adjusted P < 0.05 were used as cut-off values [16].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34901273", "locator": "sections[3] \"2.1. Protein-Protein Interaction (PPI) Network Design\" paragraph 2", "quote": "The analysis for differentially expressed genes (DEGs) was performed using the R package limma, wherein ∣log2FC | >0.5 and adjusted P < 0.05 were used as cut-off values [16]."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Previously reported gene expression data were used to support this study and are available at doi:10.1038/ejhg.2013.209 and doi:10.1016/j.ygeno.2011.06.008. These prior studies (and datasets) are cited at relevant places within the text as references [11]; [12].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34901273", "locator": "sections[9] \"Data Availability\" paragraph 2", "quote": "Previously reported gene expression data were used to support this study and are available at doi:10.1038/ejhg.2013.209 and doi:10.1016/j.ygeno.2011.06.008. These prior studies (and datasets) are cited at relevant places within the text as references [11]; [12]."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Differential-expression analysis identified 1,075 DEGs in bronchial epithelium and 47 DEGs in rectal epithelium from CF patients homozygous for p.Phe508del.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:34901273", "locator": "sections[7] \"3. Results and Discussion\" paragraph 2", "quote": "For bronchial epithelium, a total of 1075 DEGs were identified, wherein 200 genes were found to be overexpressed, and 875 genes were underexpressed."}, {"asset": "source:pmid:34901273", "locator": "sections[7] \"3. Results and Discussion\" paragraph 2", "quote": "In case of the rectal epithelium, 47 DEGs were identified, wherein 44 were overexpressed, while three genes were underexpressed genes (Figure 1(b))."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Differential-expression analysis identified 1,075 DEGs in bronchial epithelium and 47 DEGs in rectal epithelium from CF patients homozygous for p.Phe508del.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:34901273"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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